Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
J Thromb Haemost. 2012 Mar;10(3):368-74. doi: 10.1111/j.1538-7836.2012.04624.x.
Unfractionated heparin (UFH) is a widely used anticoagulant. Current American College of Chest Physicians guidelines for infants extrapolated from adults recommend 28 U kg(-1) h(1) of UFH to achieve an anti-factor Xa level of 0.35-0.7 IU mL(-1).
To assess the profile of anti-FXa-based UFH dosing guidelines in infants.
PATIENTS/METHODS: We included all infants aged < 6 months treated with per-protocol intravenous UFH at the Hospital for Sick Children, Toronto, over a 3.5-year period.
Of 100 infants, 11% achieved sustained therapeutic anti-FXa levels with current dose recommendations. Only 15% achieved target anti-FXa levels within 24 h with per-protocol dose escalations. Seventeen per cent of patients never achieved therapeutic anti-FXa levels, despite up to 60 days of therapy and triple the recommended dose. The median dose needed to achieve therapeutic anti-FXa levels in the remaining 83 infants was 33 U kg(-1) h(-1) (interquartile range, 30-36). Two in three infants had decreased thrombus size at completion of therapy and no thrombus progression/recurrence, and 11/100 infants suffered major bleeding. Without exclusion of extracorporeal membrane oxygenation patients, an activated partial thromboplastin time (APTT) of > 180 s was detected as a risk factor for major bleeding.
UFH monitoring is challenging in infants. Despite their delay in reaching therapeutic anti-FXa levels, infants monitored with the adult-based anti-FXa range have a high thrombus resolution rate, no thrombus progression, but a relatively high bleeding rate. Extreme APTT elevation may contribute to this bleeding risk, particularly in critically ill patients. Current UFH guidelines for young infants may still be inadequate, and laboratory methods with age-appropriate ranges may be required to further improve clinical outcomes within this population.
未分级肝素（UFH）是一种广泛使用的抗凝剂。目前美国胸科医师学会为婴儿制定的指南是根据成年人的研究结果外推而来，建议 UFH 的剂量为 28 U/kg·h，以达到抗因子 Xa 水平 0.35-0.7 IU/mL。
评估基于抗 FXa 的 UFH 剂量指南在婴儿中的应用情况。
患者/方法：我们纳入了多伦多 SickKids 医院在 3.5 年期间所有接受按方案静脉 UFH 治疗的年龄<6 个月的婴儿。
在 100 例婴儿中，仅 11%的婴儿能够持续达到目前剂量建议的治疗性抗 FXa 水平。只有 15%的婴儿在按方案增加剂量后 24 h 内达到目标抗 FXa 水平。尽管接受了长达 60 天的治疗和增加至推荐剂量的 3 倍，仍有 17%的患者从未达到治疗性抗 FXa 水平。其余 83 例婴儿中，中位数达到治疗性抗 FXa 水平所需的剂量为 33 U/kg·h（四分位间距，30-36）。三分之二的婴儿在完成治疗时血栓大小减小，没有血栓进展/复发，11/100 例婴儿发生大出血。不排除体外膜氧合患者，活化部分凝血活酶时间（APTT）>180 s 被认为是大出血的危险因素。
UFH 监测在婴儿中具有挑战性。尽管婴儿达到治疗性抗 FXa 水平的时间延迟，但根据成人范围内的抗 FXa 监测的婴儿血栓溶解率高，无血栓进展，但出血率相对较高。APTT 极度升高可能会增加这种出血风险，尤其是在重症婴儿中。目前针对小婴儿的 UFH 指南可能仍然不足，可能需要具有年龄相关范围的实验室方法来进一步改善该人群的临床结局。
